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Current Drug Therapy

Editor-in-Chief

ISSN (Print): 1574-8855
ISSN (Online): 2212-3903

Review Article

CORONAVIRUS and COVID-19: A Systematic Review and Perspective

Author(s): Harshal Ashok Pawar*, Anjali Harshal Pawar, Sandip Ashok Pawar and Prashant Ashok Pawar

Volume 15, Issue 5, 2020

Page: [423 - 435] Pages: 13

DOI: 10.2174/1574885515999200719142835

Price: $65

Abstract

Coronavirus (CoV) is an enveloped positive-sense RNA virus. Coronavirus disease 2019 (COVID-19) is an acute respiratory disease, induced by a new type of coronavirus, SARS-CoV-2. COVID-19 has originated in China and spread quickly all over the world. WHO acknowledged the outbreak of a global pandemic on March 11, 2020. The spread of COVID-19 signified a big threat to social life, the economy, and public health. As of April 14, 2020, WHO reported a total of 1,812,734 confirmed cases of COVID-19 and 113,675 (6.27 %) deaths throughout the world. Numerous nations around the globe took assorted measures because of the danger of SARS-CoV-2 and created wide-ranging preventive approaches. No particular drug or vaccines/antibodies are yet accessible for the treatment of this unforeseen and lethal illness. The pandemic has brought about travel limitations and across the country lockdowns in most of the nations. The objective behind this article was to provide recent updates and well-authenticated information to the scientific community, health care personnel’s and common public about Coronavirus, their types, characteristic features, structure and origin, mode of transmission, pathogenesis, clinical symptoms, diagnostic methods, drug development approach, prevention and treatment of COVID-19.

Keywords: COVID-19, SARS-CoV-2, MERS-CoV, coronavirus, antiviral drugs, RNA.

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[1]
Fehr AR, Perlman S. Coronaviruses: an overview of their replication and pathogenesis. Coronaviruses New York, NY: Humana Press 2015; pp. 1-23.
[http://dx.doi.org/10.1007/978-1-4939-2438-7_1]
[2]
Zhang L, Lin D, Sun X, et al. Crystal structure of SARS-CoV-2 main protease provides a basis for design of improved α-ketoamide inhibitors. Science 2020; 368(6489): 409-12.
[http://dx.doi.org/10.1126/science.abb3405] [PMID: 32198291]
[3]
Coronavirus disease (COVID-19) Situation Dashboard. Available from: https://www.who.int/emergencies/diseases/novel-coronavirus-20192020 01/04/2020
[4]
Kampf G, Todt D, Pfaender S, Steinmann E. Persistence of coronaviruses on inanimate surfaces and their inactivation with biocidal agents. J Hosp Infect 2020; 104(3): 246-51.
[http://dx.doi.org/10.1016/j.jhin.2020.01.022] [PMID: 32035997]
[5]
Guo YR, Cao QD, Hong ZS, et al. The origin, transmission and clinical therapies on coronavirus disease 2019 (COVID-19) outbreak–an update on the status. Mil Med Res 2020; 7(1): 1-0.
[http://dx.doi.org/10.1186/s40779-020-00240-0] [PMID: 31928528]
[6]
Zumla A, Chan JF, Azhar EI, Hui DS, Yuen KY. Coronaviruses - drug discovery and therapeutic options. Nat Rev Drug Discov 2016; 15(5): 327-47.
[http://dx.doi.org/10.1038/nrd.2015.37] [PMID: 26868298]
[7]
Xie X, Zhong Z, Zhao W, Zheng C, Wang F, Liu J. Chest CT for typical (COVID-19) pneumonia: relationship to negative RT-PCR testing. Radiology 2020; 296(2): E41-5.
[http://dx.doi.org/10.1148/radiol.2020200343] [PMID: 32049601]
[8]
Li G, De Clercq E. Therapeutic options for the 2019 novel coronavirus (2019-nCoV). 2020; 19(3): 149-50.
[9]
Liu J, Manheimer E, Shi Y, Gluud C. Chinese herbal medicine for severe acute respiratory syndrome: a systematic review and meta-analysis. J Altern Complement Med 2004; 10(6): 1041-51.
[http://dx.doi.org/10.1089/acm.2004.10.1041] [PMID: 15674000]
[10]
Sarma P, Prajapat M, Avti P, Kaur H, Kumar S, Medhi B. Therapeutic options for the treatment of 2019-novel coronavirus: An evidence-based approach. Indian J Pharmacol 2020; 52(1): 1-5.
[http://dx.doi.org/10.4103/ijp.IJP_119_20] [PMID: 32201439]
[11]
Li T, Peng T. Traditional Chinese herbal medicine as a source of molecules with antiviral activity. Antiviral Res 2013; 97(1): 1-9.
[http://dx.doi.org/10.1016/j.antiviral.2012.10.006] [PMID: 23153834]
[12]
Available from: https://en.m.wikipedia.org/wiki/Coronavirus Accessed on April 16, 2020.
[13]
File:3D medical animation corona virusjpg. Available from: https://commons.wikimedia.org/wiki/File:3D_medical_animation_corona_virus.jpg (Accessed on April 02, 2020)
[14]
Goldsmith CS, Tatti KM, Ksiazek TG, et al. Ultrastructural characterization of SARS coronavirus. Emerg Infect Dis 2004; 10(2): 320-6.
[http://dx.doi.org/10.3201/eid1002.030913] [PMID: 15030705]
[15]
Lai MM, Cavanagh D. The molecular biology of coronaviruses. Adv Virus Res 1997; 48: 1-100.
[http://dx.doi.org/10.1016/S0065-3527(08)60286-9] [PMID: 9233431]
[16]
Beniac DR, Andonov A, Grudeski E, Booth TF. Architecture of the SARS coronavirus prefusion spike. Nat Struct Mol Biol 2006; 13(8): 751-2.
[http://dx.doi.org/10.1038/nsmb1123] [PMID: 16845391]
[17]
Bosch BJ, van der Zee R, de Haan CA, Rottier PJ. The coronavirus spike protein is a class I virus fusion protein: structural and functional characterization of the fusion core complex. J Virol 2003; 77(16): 8801-11.
[http://dx.doi.org/10.1128/JVI.77.16.8801-8811.2003] [PMID: 12885899]
[18]
Neuman BW, Kiss G, Kunding AH, et al. A structural analysis of M protein in coronavirus assembly and morphology. J Struct Biol 2011; 174(1): 11-22.
[http://dx.doi.org/10.1016/j.jsb.2010.11.021] [PMID: 21130884]
[19]
Nal B, Chan C, Kien F, et al. Differential maturation and subcellular localization of severe acute respiratory syndrome coronavirus surface proteins S, M and E. J Gen Virol 2005; 86(Pt 5): 1423-34.
[http://dx.doi.org/10.1099/vir.0.80671-0] [PMID: 15831954]
[20]
Nieto-Torres JL, DeDiego ML, Verdiá-Báguena C, et al. Severe acute respiratory syndrome coronavirus envelope protein ion channel activity promotes virus fitness and pathogenesis. PLoS Pathog 2014; 10(5)e1004077
[http://dx.doi.org/10.1371/journal.ppat.1004077] [PMID: 24788150]
[21]
Hurst KR, Koetzner CA, Masters PS. Identification of in vivo-interacting domains of the murine coronavirus nucleocapsid protein. J Virol 2009; 83(14): 7221-34.
[http://dx.doi.org/10.1128/JVI.00440-09] [PMID: 19420077]
[22]
Cornelissen LA, Wierda CM, van der Meer FJ, et al. Hemagglutinin-esterase, a novel structural protein of torovirus. J Virol 1997; 71(7): 5277-86.
[http://dx.doi.org/10.1128/JVI.71.7.5277-5286.1997] [PMID: 9188596]
[23]
Lauber C, Ziebuhr J, Junglen S, et al. Mesoniviridae: a proposed new family in the order Nidovirales formed by a single species of mosquito-borne viruses. Arch Virol 2012; 157(8): 1623-8.
[http://dx.doi.org/10.1007/s00705-012-1295-x] [PMID: 22527862]
[24]
Perlman S, Netland J. Coronaviruses post-SARS: update on replication and pathogenesis. Nat Rev Microbiol 2009; 7(6): 439-50.
[http://dx.doi.org/10.1038/nrmicro2147] [PMID: 19430490]
[25]
He B, Zhang Y, Xu L, et al. Identification of diverse alphacoronaviruses and genomic characterization of a novel severe acute respiratory syndrome-like coronavirus from bats in China. J Virol 2014; 88(12): 7070-82.
[http://dx.doi.org/10.1128/JVI.00631-14] [PMID: 24719429]
[26]
Mihindukulasuriya KA, Wu G, St Leger J, Nordhausen RW, Wang D. Identification of a novel coronavirus from a beluga whale by using a panviral microarray. J Virol 2008; 82(10): 5084-8.
[http://dx.doi.org/10.1128/JVI.02722-07] [PMID: 18353961]
[27]
Wu GF, Perlman S. Macrophage infiltration, but not apoptosis, is correlated with immune-mediated demyelination following murine infection with a neurotropic coronavirus. J Virol 1999; 73(10): 8771-80.
[http://dx.doi.org/10.1128/JVI.73.10.8771-8780.1999] [PMID: 10482631]
[28]
Weiner LP. Pathogenesis of demyelination induced by a mouse hepatitis. Arch Neurol 1973; 28(5): 298-303.
[http://dx.doi.org/10.1001/archneur.1973.00490230034003] [PMID: 4348723]
[29]
Liu P, Shi L, Zhang W, et al. Prevalence and genetic diversity analysis of human coronaviruses among cross-border children. Virol J 2017; 14(1): 230.
[http://dx.doi.org/10.1186/s12985-017-0896-0] [PMID: 29166910]
[30]
Corman VM, Muth D, Niemeyer D, Drosten C. Hosts and sources of endemic human coronaviruses. Adv Virus Res 2018; 100: 163-88.
[http://dx.doi.org/10.1016/bs.aivir.2018.01.001] [PMID: 29551135]
[31]
Yin Y, Wunderink RG. MERS, SARS and other coronaviruses as causes of pneumonia. Respirology 2018; 23(2): 130-7.
[http://dx.doi.org/10.1111/resp.13196] [PMID: 29052924]
[32]
Zhou P, Yang XL, Wang XG, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 2020; 579(7798): 270-3.
[http://dx.doi.org/10.1038/s41586-020-2012-7] [PMID: 32015507]
[33]
Guan WJ, Ni ZY, Hu Y, et al. China Medical Treatment Expert Group for Covid-19. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med 2020; 382(18): 1708-20.
[http://dx.doi.org/10.1056/NEJMoa2002032] [PMID: 32109013]
[34]
Kang CK, Song KH, Choe PG, et al. Clinical and epidemiologic characteristics of spreaders of middle east respiratory syndrome coronavirus during the 2015 outbreak in Korea. J Korean Med Sci 2017; 32(5): 744-9.
[http://dx.doi.org/10.3346/jkms.2017.32.5.744] [PMID: 28378546]
[35]
COVID-19 treatment might already exist in old drugs-we’re using pieces of the coronavirus itself to find them. Available from: http://theconversation.com/covid-19-treatment-might-already-exist-in-old-drugs-were-using-pieces-of-the-coronavirus-itself-to-find-them-133701 (Accessed on April 02, 2020)
[36]
Wang W, Tang J, Wei F. Updated understanding of the outbreak of 2019 novel coronavirus (2019-nCoV) in Wuhan, China. J Med Virol 2020; 92(4): 441-7.
[http://dx.doi.org/10.1002/jmv.25689] [PMID: 31994742]
[37]
Yang X, Yu Y, Xu J, et al. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. Lancet Respir Med 2020; 8(5): 475-81.
[http://dx.doi.org/10.1016/S2213-2600(20)30079-5] [PMID: 32105632]
[38]
Available from: https://en.wikipedia.org/wiki/COVID-19_testing (Accessed on April 16, 2020)
[39]
Li Z, Yi Y, Luo X, et al. Development and clinical application of a rapid IgM-IgG combined antibody test for SARS-CoV-2 infection diagnosis. J Med Virol 2020; 92(9): 1518-24.
[http://dx.doi.org/10.1002/jmv.25727] [PMID: 32104917]
[40]
Ai T, Yang Z, Hou H, et al. Correlation of chest CT and RT-PCR testing in coronavirus disease 2019 (COVID-19) in China: a report of 1014 cases. Radiology 2020; 296(2): E32-40.
[http://dx.doi.org/10.1148/radiol.2020200642] [PMID: 32101510]
[41]
Carlos WG, Dela Cruz CS, Cao B, Pasnick S, Jamil S. Novel Wuhan (2019-nCoV) Coronavirus. Am J Respir Crit Care Med 2020; 201(4): 7-P8.
[http://dx.doi.org/10.1164/rccm.2014P7] [PMID: 32004066]
[42]
Yang Y, Islam MS, Wang J, Li Y, Chen X. Traditional Chinese medicine in the treatment of patients infected with 2019-new Coronavirus (SARS-CoV-2): a review and perspective. Int J Biol Sci 2020; 16(10): 1708-17.
[http://dx.doi.org/10.7150/ijbs.45538] [PMID: 32226288]
[43]
Li H, Wang YM, Xu JY, Cao B. Potential antiviral therapeutics for 2019 Novel Coronavirus. Zhonghua Jie He He Hu Xi Za Zhi 2020; 43E002
[PMID: 32023685]
[44]
Lim J, Jeon S, Shin HY, et al. Case of the index patient who caused tertiary transmission of COVID-19 infection in Korea: the application of lopinavir/ritonavir for the treatment of COVID-19 infected pneumonia monitored by quantitative RT-PCR. J Korean Med Sci 2020; 35(6)e79
[http://dx.doi.org/10.3346/jkms.2020.35.e79] [PMID: 32056407]
[45]
Wang Z, Chen X, Lu Y, Chen F, Zhang W. Clinical characteristics and therapeutic procedure for four cases with 2019 novel coronavirus pneumonia receiving combined Chinese and Western medicine treatment. Biosci Trends 2020; 14(1): 64-8.
[http://dx.doi.org/10.5582/bst.2020.01030] [PMID: 32037389]
[46]
Chen N, Zhou M, Dong X, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet 2020; 395(10223): 507-13.
[http://dx.doi.org/10.1016/S0140-6736(20)30211-7] [PMID: 32007143]
[47]
Jordan PC, Stevens SK, Deval J. Nucleosides for the treatment of respiratory RNA virus infections. Antivir Chem Chemother 2018; 262040206618764483
[http://dx.doi.org/10.1177/2040206618764483] [PMID: 29562753]
[48]
De Clercq E. New Nucleoside Analogues for the Treatment of Hemorrhagic Fever Virus Infections. Chem Asian J 2019; 14(22): 3962-8.
[http://dx.doi.org/10.1002/asia.201900841] [PMID: 31389664]
[49]
Wang M, Cao R, Zhang L, et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res 2020; 30(3): 269-71.
[http://dx.doi.org/10.1038/s41422-020-0282-0] [PMID: 32020029]
[50]
Sheahan TP, Sims AC, Graham RL, et al. Broad-spectrum antiviral GS-5734 inhibits both epidemic and zoonotic coronaviruses. Sci Transl Med 2017; 9(396): 9.
[http://dx.doi.org/10.1126/scitranslmed.aal3653] [PMID: 28659436]
[51]
Zhang L, Liu Y. Potential interventions for novel coronavirus in china: a systemic review. J Med Virol 2020; 92(5): 479-90.
[http://dx.doi.org/10.1002/jmv.25707]
[52]
Holshue ML, DeBolt C, Lindquist S, et al. Washington State 2019-nCoV case investigation team. First case of 2019 novel Coronavirus in the United States. N Engl J Med 2020; 382(10): 929-36.
[http://dx.doi.org/10.1056/NEJMoa2001191] [PMID: 32004427]
[53]
Lai CC, Shih TP, Ko WC, Tang HJ, Hsueh PR. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease-2019 (COVID-19): The epidemic and the challenges. Int J Antimicrob Agents 2020; 55(3)105924
[http://dx.doi.org/10.1016/j.ijantimicag.2020.105924] [PMID: 32081636]
[54]
Cinatl J, Morgenstern B, Bauer G, Chandra P, Rabenau H, Doerr HW. Treatment of SARS with human interferons. Lancet 2003; 362(9380): 293-4.
[http://dx.doi.org/10.1016/S0140-6736(03)13973-6] [PMID: 12892961]
[55]
Stockman LJ, Bellamy R, Garner P. SARS: systematic review of treatment effects. PLoS Med 2006; 3(9)e343
[http://dx.doi.org/10.1371/journal.pmed.0030343] [PMID: 16968120]
[56]
Jin YH, Cai L, Cheng ZS, et al. for the Zhongnan Hospital of Wuhan University novel Coronavirus management and research team, evidence-based medicine chapter of China International Exchange and Promotive Association for Medical and Health Care (CPAM). A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version). Mil Med Res 2020; 7(1): 4.
[http://dx.doi.org/10.1186/s40779-020-0233-6] [PMID: 32029004]
[57]
Habibzadeh P, Stoneman EK. The novel Coronavirus: a Bird’s eye view. Int J Occup Environ Med 2020; 11(2): 65-71.
[http://dx.doi.org/10.15171/ijoem.2020.1921] [PMID: 32020915]
[58]
Laude H, Van Reeth K, Pensaert M. Porcine respiratory coronavirus: molecular features and virus-host interactions. Vet Res 1993; 24(2): 125-50.
[PMID: 8393722]
[59]
Vennema H, de Groot RJ, Harbour DA, et al. Early death after feline infectious peritonitis virus challenge due to recombinant vaccinia virus immunization. J Virol 1990; 64(3): 1407-9.
[http://dx.doi.org/10.1128/JVI.64.3.1407-1409.1990] [PMID: 2154621]
[60]
Züst R, Cervantes-Barragán L, Kuri T, et al. Coronavirus non-structural protein 1 is a major pathogenicity factor: implications for the rational design of coronavirus vaccines. PLoS Pathog 2007; 3(8)e109
[http://dx.doi.org/10.1371/journal.ppat.0030109] [PMID: 17696607]
[61]
Netland J, DeDiego ML, Zhao J, et al. Immunization with an attenuated severe acute respiratory syndrome coronavirus deleted in E protein protects against lethal respiratory disease. Virology 2010; 399(1): 120-8.
[http://dx.doi.org/10.1016/j.virol.2010.01.004] [PMID: 20110095]
[62]
de Haan CA, Volders H, Koetzner CA, Masters PS, Rottier PJ. Coronaviruses maintain viability despite dramatic rearrangements of the strictly conserved genome organization. J Virol 2002; 76(24): 12491-502.
[http://dx.doi.org/10.1128/JVI.76.24.12491-12502.2002] [PMID: 12438575]
[63]
Yount B, Roberts RS, Lindesmith L, Baric RS. Rewiring the severe acute respiratory syndrome coronavirus (SARS-CoV) transcription circuit: engineering a recombination-resistant genome. Proc Natl Acad Sci USA 2006; 103(33): 12546-51.
[http://dx.doi.org/10.1073/pnas.0605438103] [PMID: 16891412]
[64]
Graham RL, Becker MM, Eckerle LD, Bolles M, Denison MR, Baric RS. A live, impaired-fidelity coronavirus vaccine protects in an aged, immunocompromised mouse model of lethal disease. Nat Med 2012; 18(12): 1820-6.
[http://dx.doi.org/10.1038/nm.2972] [PMID: 23142821]
[65]
Cortegiani A, Ingoglia G, Ippolito M, Giarratano A, Einav S. A systematic review on the efficacy and safety of chloroquine for the treatment of COVID-19. J Crit Care 2020; 57: 279-83.
[http://dx.doi.org/10.1016/j.jcrc.2020.03.005] [PMID: 32173110]
[66]
Gao J, Tian Z, Yang X. Breakthrough: Chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies. Biosci Trends 2020; 14(1): 72-3.
[http://dx.doi.org/10.5582/bst.2020.01047] [PMID: 32074550]
[67]
Colson P, Rolain J-M, Raoult D. Chloroquine for the 2019 novel coronavirus SARS-CoV-2. Int J Antimicrob Agents 2020; 55(3)105923
[http://dx.doi.org/10.1016/j.ijantimicag.2020.105923] [PMID: 32070753]
[68]
Aguiar ACC, Murce E, Cortopassi WA, et al. Chloroquine analogs as antimalarial candidates with potent in vitro and in vivo activity. Int J Parasitol Drugs Drug Resist 2018; 8(3): 459-64.
[http://dx.doi.org/10.1016/j.ijpddr.2018.10.002] [PMID: 30396013]
[69]
Savarino A, Boelaert JR, Cassone A, Majori G, Cauda R. Effects of chloroquine on viral infections: an old drug against today’s diseases? Lancet Infect Dis 2003; 3(11): 722-7.
[http://dx.doi.org/10.1016/S1473-3099(03)00806-5] [PMID: 14592603]
[70]
Vincent MJ, Bergeron E, Benjannet S, et al. Chloroquine is a potent inhibitor of SARS coronavirus infection and spread. Virol J 2005; 2: 69.
[http://dx.doi.org/10.1186/1743-422X-2-69] [PMID: 16115318]
[71]
Golden EB, Cho HY, Hofman FM, Louie SG, Schönthal AH, Chen TC. Quinoline-based antimalarial drugs: a novel class of autophagy inhibitors. Neurosurg Focus 2015; 38(3)E12
[http://dx.doi.org/10.3171/2014.12.FOCUS14748] [PMID: 25727221]
[72]
Yao X, Ye F, Zhang M, et al. In vitro antiviral activity and projection of optimized dosing design of hydroxychloroquine for the reatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Clin Infect Dis 2020.ciaa237
[http://dx.doi.org/10.1093/cid/ciaa237] [PMID: 32150618]
[73]
He L, Ding Y, Zhang Q, et al. Expression of elevated levels of pro-inflammatory cytokines in SARS-CoV-infected ACE2+ cells in SARS patients: relation to the acute lung injury and pathogenesis of SARS. J Pathol 2006; 210(3): 288-97.
[http://dx.doi.org/10.1002/path.2067] [PMID: 17031779]
[74]
Faure E, Poissy J, Goffard A, et al. Distinct immune response in two MERS-CoV-infected patients: can we go from bench to bedside? PLoS One 2014; 9(2)e88716
[http://dx.doi.org/10.1371/journal.pone.0088716] [PMID: 24551142]
[75]
Veronese N, Demurtas J, Yang L, et al. Use of corticosteroids in Coronavirus Disease 2019 Pneumonia: a systematic review of the literature. Front Med 2020; 7: 170.
[http://dx.doi.org/10.3389/fmed.2020.00170] [PMID: 32391369]
[76]
Lansbury L, Rodrigo C, Leonardi-Bee J, Nguyen-Van-Tam J, Lim WS. Corticosteroids as adjunctive therapy in the treatment of influenza. Cochrane Database Syst Rev 2019; 2(2)2CD010406
[http://dx.doi.org/10.1002/14651858.CD010406.pub3] [PMID: 30798570]
[77]
Arabi YM, Mandourah Y, Al-Hameed F, et al. Saudi critical care trial group. Corticosteroid therapy for critically Ill Patients with Middle East respiratory syndrome. Am J Respir Crit Care Med 2018; 197(6): 757-67.
[http://dx.doi.org/10.1164/rccm.201706-1172OC] [PMID: 29161116]
[78]
Russell CD, Millar JE, Baillie JK. Clinical evidence does not support corticosteroid treatment for 2019-nCoV lung injury. Lancet 2020; 395(10223): 473-5.
[http://dx.doi.org/10.1016/S0140-6736(20)30317-2] [PMID: 32043983]
[79]
Hannah Slater. FDA approves Phase III clinical trial of tocilizumab for COVID-19 pneumonia Cancer Network, MJH. Life Sci 2020; (March): 26. Retrieved 28 March 2020.

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